Propofol injection pain is alleviated by decreased free concentration in the admixture with flurbiprofen axetil emulsion.

Ryusuke UEKI, Masaaki TANIMOTO, Tsuneo TATARA, Yoshiroh KAMINOH, Chikara TASHIRO

Department of Anesthesiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan

 

Introduction:   Dilution of propofol emulsion with additional 10% soybean oil (Intralipid^®) was reported to reduce injection pain, probably because of a decreased concentration of free propofol in the aqueous phase.  In Japan, two propofol formulations are commercially available, namely 1% Diprivan^® AstraZeneka (Pa) containing 10 % soybean oil, and 1% propofol-Lipuro^® B.Brown (Pb) containing 5% medium-chain triglycerides with 5% soybean oil.  Flurbiprofen axetil (FP) 50mg/5ml, a prodrug of an NSAID, is popular for perioperative pain relief in our country and its formulation also contains 10% soybean oil.  Therefore we compared each propofol formulation with the admixture of each propofol formulation (15ml) with 5ml FP emulsion or saline (S) in terms of injection pain score and free propofol concentration of the mixed emulsion.

Methods:  After obtaining institutional review board’s approval and oral informed consent, 300 patients (ASA 1-2, age 20-70 yr) scheduled for the elective operation were randomly assigned to either of six groups.  Anesthesia was induced with 2 mg/kg propofol in each group (n=50) given; (1) plain Pa, (2) Pa＋S, (3) Pa＋FP, (4) plain Pb, (5) Pb＋S, or (6) Pb＋FP.  One researcher blinded to group assignment asked the patients to evaluate the pain (0=none, 1=mild, 2=moderate, 3=severe) every 10 seconds after the start of 1 min bolus injection (Grasby 3500 pump). Time to sleep was also recorded.  The free propofol concentration of each emulsion was measured with HPLC method after 24 hours dialysis (MWCO 3500, Bio-Tech International, Inc).

Results:  The incidence of injection pain was 70% in Pa, 62% in Pa+S, 54% in Pa+FP, 58% in Pb, 42% in Pb+S, and 30% in Pb+FP group respectively.  As the control of the pain incidence in Pa, Number Need to treat was 12.5 in Pa+S, 6.25 in Pa+FP, 8.3 in Pb, 3.6 in Pb+S, and 2.5 in Pb+FP group respectively.  Free propofol concentration (μg/ml) was 15.5+0.3 in Pa, 14.6+0.5 in Pa+S, 10.7+0.3 in Pa+FP, 11.6+0.4 in Pb, 10.2+0.6 in Pb+S, and 7.3+0.2 in Pb+FP group respectively (mean+SD).  The admixture with FP emulsion significantly reduced injection pain in Pb (P<0.01).  When incidence of injection pain was plotted against free propofol concentration in 6 groups, each point was well fitted to the dose-response curve, and the ED50 was 10.7μg/ml.

Discussion & Conclusion:  Low concentration of free propofol decreased the incidence of pain on injection.  Although flurbiporofen was expected to reduce pain by anti-inflammatory action, it will take several minutes or more to exert its analgesic action after converting active form.   The admixture of propofol formulation with additional flurbiprofen emulsion is simple and time-saving method for the prevention of injection pain.